Expression of heterologous genes such as B type hepatitis virus surface antigen or HBsAg, IFN-.alpha., etc. in yeast has been carried out. It is known that the mechanism of control on the yeast promoter is generally a positive control. In connection with this positive control, the existence of an upstream activation site (UAS), which is located several hundreds bases upstream of the initiation point of translation and which functions in a cis-sequence, has been suggested as a controlling factor of the promoter, (see L. Guarente, Cell, 36, 799 (1984)). It has been found that replacement of the UAS with a different UAS releases the promoter from its normal control system. That is, the promoter comes under the control of the new UAS (see L. Guarente et al., Proc. Natl. Acd. Sci., USA, 79, 7410 (1982), L. Guarante et al., Cell, 36, 503 (1984), K. Struhl, Proc. Natl. Acd. Sci., 81, 7865 (1984).
Yeast promoters include the glyceraldehyde-3phosphate dehydrogenase (GAP-DH) promoter, which is utilized for a plasmid producing B type hepatitis virus surface antigen (HBsAg). For example, Bittler, G. A. & Egan, K. M., Gene, 32, 263-274 (1984) describes the expression of heterologous genes in Saccharomyces cerevisiae from an expression vector utilizing the GAP-DH gene promoter, and EP-A-120,551 corresponding to JP-A-210888/84 describes a yeast expression vector and a method of its use.
For example, as described in Reference Example 1 below, the HBsAg-producing plasmid pGG5 was constructed using the GAP-DH promoter, the HBsAg structural gene, the GAP-DH terminator, a replication initiator point of E. coli, marker genes (e.g., the ampicillin-resistant gene (Apc) in E. coli and the leucine gene in yeast) and a replication initiator point in yeast.